核苷(酸)类抗病毒药物对失代偿期乙型肝炎肝硬化患者肾功能的影响研究

Effects of nucleos(t)ide analogues on renal functions in patients with Hepatitis B virus-induced decompensated liver cirrhosis

目的评价核苷(酸)类药物(NUCs)对失代偿期乙型肝炎肝硬化患者肾功能的影响。方法纳入失代偿期乙型肝炎肝硬化患者306例,其中接受抗病毒治疗者中包括拉米夫定(LAM)治疗者39例、阿德福韦(ADV)73例、替比夫定(LDT)34例、恩替卡韦(ETV)48例、LAM联合ADV 41例、LDT联合ADV 25例和未抗病毒治疗对照46例。随访3年。排除失访、随访时间小于3年和对照组中途开始抗病毒治疗者97例,最终209例患者纳入本研究。观察估算的肾小球滤过率(eGFR)、血清肌酐和尿素氮水平变化。结果与对照组比,各抗病毒治疗组1年、2年、3年时eGFR较基线均无明显变化(P>0.05),而LDT、LDT联合ADV组eGFR有逐年升高趋势(P>0.05);本组失代偿期乙型肝炎肝硬化患者在基线时存在轻度肾功能损害者58例(27.8%);在存在轻度肾损伤(基线eGFR<90ml·min^(-1)·1.73m^(-2))的患者,经LDT或LDT联合ADV治疗3年时患者eGFR复常率分别为55.6%和50%;各组患者血清肌酐和尿素氮水平与基线比无显著性差异(P>0.05)。结论 LDT单药或联合ADV可改善失代偿期乙型肝炎肝硬化患者的肾功能。

Objective To evaluate the effect of nucleos（t）ide analogues （NUCs） on renal functions in pa-tients with hepatitis B virus（HBV）-induced decompensated liver cirrhosis. Methods In this cohort study,306 pa-tients with HBV-associated decompensated cirrhosis were assigned to receive lamivudine （LAM,n=39）,adefovir （ADV,n=73）,telbivudine （LDT,n=34）,entecavir （ETV,n=48）,LDT and ADV （n=41） or LAM and ADV（n=25） treatment for three years,and 46 patients didn’t receive antiviral therapy for control. 97 patients were excluded because of loss,followed-up less than three years,or those in control at baseline received antiviral therapy. 209 patients were followed-up every 3 to 6 months. Changes of estimated glomerular filtration rate （eGFR）,serum cre-atinine and urea nitrogen were analyzed. Results Among patients who received antiviral therapy,eGFR levels did not change significantly from baseline （P〉0.05）,but patients who received LDT or LDT and ADV combination therapy showed gradual increase in eGFR （P〉0.05）;58 patients （27.8%） had mild kidney function injuries at baseline,and the normalization rates of eGFR in patients with mild renal decrease （eGFR〈90 ml·min-1·1.73 m-2） at baseline were 55.6% and 50%,respectively in patients who were treated with LDT or LDT and ADV combina-tion;The serum creatinine and urea nitrogen levels did not obviously change in all patients. Conclusion LDT monotherapy or in combination with ADV is associated with improved renal function in patients with HBV-associ-ated decompensated cirrhosis.